Published on Web 04/11/2008
Isolation and Characterization of a Neutral Imino-semiquinone Radical Shawn M. Carter, Allyson Sia, Michael J. Shaw,* and Alan F. Heyduk* Department of Chemistry, UniVersity of California, IrVine, California, 92697, and Department of Chemistry, Southern Illinois UniVersity EdwardsVille, EdwardsVille, Illinois 62026 Received December 17, 2007; E-mail:
[email protected];
[email protected] Quinone and semiquinone molecules play an important role in organic synthesis, metal coordination chemistry, and biological chemistry.1 For example, copper amine oxidases (CAOs) use quinone-derived cofactors in the aerobic oxidative deamination catalysis of amines. Recent studies of CAOs have shown that o-aminophenols and o-iminoquinones are formed during the copper-catalyzed conversions of primary amines to aldehydes,2 and short-lived imino-semiquinone intermediates have been observed during mechanistic studies. It has been speculated that imino-semiquinone formation occurs by the conproportionation of iminoquinone and aminophenol, yet this reaction has not been observed in a synthetic system.3 Herein, we report the preparation and characterization of the first stable iminosemiquinone radical (isqH•, 4,6-di-tert-butyl-2-tert-butyliminosemiquinone), along with an evaluation of the thermodynamic parameters leading to the stabilization of the imino-semiquinone relative to the iminoquinone (iq, 4,6-di-tert-butyl-2-tert-butyliminoquinone) and aminophenol (apH2, 4,6-di-tert-butyl-2-tertbutylaminophenol) congeners. The aminophenol, apH2, was used to prepare iq and isqH•. Condensation of tBuNH2 with 3,5-di-tert-butylcatechol yields apH2.4 The iminoquinone, iq, was prepared by deprotonation of apH2 with n-BuLi, followed by oxidation with PhICl2. The neutral imino-semiquinone, isqH•, was generated by the reaction of apH2 with iq according to eq 1. A dark-blue reaction solution in DMSO yielded the four-line EPR spectrum shown in Figure 1 (inset) and is consistent with the formation of the isqH• radical. The isqH• radical cocrystallized with apH2 from cold MeCN,5 and iq crystallized from cold pentane.6 Figure 1 shows the structure of the isqH• fragment along with select metrical parameters; structural details for apH2 and iq can be found in the Supporting Information.
Bond lengths within isqH• are consistent with the assigned oxidation state. Specifically, C-N and C-O bond lengths of 1.34 and 1.26 Å, respectively, are shorter than the corresponding bonds in apH2 (1.44 and 1.37 Å, respectively) but longer than those in iq (1.28 and 1.22 Å, respectively). While average C-C bond distances of 1.39 Å are consistent with fully delocalized π bonding in the aromatic ring of apH2, localization of double bond character is pronounced in the C-C bond distances of isqH• (see Figure 1). Iq is best described as a cyclohexadiene ring with fully localized C-C double bonds, as denoted by bond lengths of 1.34 Å. 5838
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Figure 1. Solid-state molecular structure of isqH• and its X-band EPR
spectrum (DMSO, 298 K; g ) 2.0061). The neutral radical cocrystallizes with apH2, which has been omitted for clarity. Selected bond lengths in Å: O1-C1 1.2577(14); N1-C2 1.3455(16); C1-C2 1.4716(17); C2-C3 1.4047(17); C3-C4 1.3747(18); C4-C5 1.4294(17); C5-C6 1.3644(17); C1-C6 1.4502(17).
The reaction used to prepare isqH• is intriguing because mixtures of catechols and quinones usually are stable toward conproportionation. For example, 1:1 mixtures of colorless 3,5di-tert-butylcatechol and red 3,5-di-tert-butyl-ortho-quinone are stable, showing no evidence for conproportionation to the semiquinone radical. Solutions of these mixtures are orange, consistent with the color of the ortho-quinone, and the 1H NMR spectrum of the mixture is a composite of the separate catechol and quinone spectra. Conversely, 1:1 mixtures of apH2 and iq afford blue solutions with a strong absorbance in the visible region. NMR spectra of these solutions are essentially featureless, consistent with paramagnetic line broadening. To elucidate the stability of the isqH• radical in different solvents, spectrophotometric titrations were conducted. Figure 2 displays the absorption data for the titration of iq with apH2 in DMSO at room temperature. Addition of apH2 gave an increase in absorbance at 734 nm, which eventually reached a plateau. Similar results were obtained for titrations of apH2 with iq. A plot of absorbance at 734 nm versus [apH2] added, shown as an inset to Figure 2, was used to extract the equilibrium or conproportionation constant of eq 1. Table 1 gives Kc values for eq 1 along with the extrapolated extinction coefficient for isqH• at 734 nm in several solvents. Similar equilibrium constants were obtained when the titrations were carried out in 1 M HCl solutions of DMSO or MeCN. Electrochemical and acid-base studies were used to examine the thermodynamic parameters leading to the formation of isqH•. 10.1021/ja711185s CCC: $40.75 2008 American Chemical Society
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Scheme 1. Electrochemical (vs Cp2Fe
Relating apH2, isqH•, and iq in DMSO
Figure 2. Changes in the electronic absorption spectrum during titration of a DMSO solution of iq (0.186 mM) with 1.59 mM apH2 (inset: absorbance at 734 nm as a function of added apH2). •
Table 1. Spectral Data and Conproportionation Constants for isqH
in Various Solvents solvent
734 nm/M-1 cm-1
Kc
C6H5Me MeCN CH2Cl2 DMSO
929 859 901 710
20 9 10 5.75
Previous studies by Bordwell and co-workers7 have shown that the homolytic bond dissociation energies (BDEs) can be calculated from the energy of electron (E°′) and proton (pKa) transfer processes according to eq 2.8,9 Although it is actually the free energy (∆G) of the bond dissociation that is being calculated, this energy approximates the bond dissociation energy (∆U) assuming negligible entropic or work contributions. EHAT ) 23.06E ° ′ + 1.37pKa + C
(2)
The one-electron redox potentials of the blue semiquinone radical were readily obtained.6 DMSO solutions of isqH• yielded reversible, one-electron redox features by cyclic voltammetry that were absent in solutions of pure apH2 or pure iq. A oneelectron oxidation was observed for isqH• at E°′(ox) ) -0.112 V vs Cp2Fe0/+, while a one-electron reduction was observed at E°′(red) ) -0.924 V vs Cp2Fe0/+. Under similar conditions, apH2 showed a partially reversible one-electron oxidation at +0.06 V vs Cp2Fe0/+ and iq showed a partially reversible oneelectron reduction at -1.368 V vs Cp2Fe0/+. The pKa values for apH2 and iqH+ in DMSO were estimated from spectrophotometric titrations. Saccharin (pKa = 4.0 in DMSO)10 proved to be a suitable acid for the protonation of iq and afforded a pKa of 3.8 for iqH+.11 Titration of apH2 with [Bu4N][NHCOCF3] (pKa of NH2COCF3 = 17.2 in DMSO)10,12 gave a pKa of 18.0, which is similar to the pKa of phenol in DMSO.13 The thermodynamic data summarized in Scheme 1 suggest that the tert-butylimino group is responsible for the stability of isqH•. The calculated energy for the removal of a hydrogen atom from apH2 (76.7 kcal mol-1) is similar to the literature value for 3,5di-tert-butylcatechol (78.2 kcal mol-1),14 suggesting that a weak BDE in apH2 is not responsible for the ready formation of isqH•. Instead, the key feature stabilizing isqH• appears to be the basicity of the tert-butylimino group. According to the solid-state X-ray
) and pKa Measurements
diffraction data, the active proton of isqH• is bound to the nitrogen and forms a hydrogen bond to the oxygen, giving the orthoiminium phenoxide zwitterionic structure drawn in eq 1. Accordingly, isqH• is both a poor Bro¨nsted acid and a poor Bro¨nsted base.15 The lack of a basic site in isqH• is reflected in the pKa of (isqH2•)+, which is estimated to be 1.5 according to the HAT energy in Scheme 1. Furthermore, the hydrogen-bonded imminium proton has a high estimated pKa of 25, which is significantly less acidic than the corresponding 3,5-di-tert-butyl-ortho-semiquinone radical (pKa = 6.0 in aqueous solution).16 Acknowledgment. The authors thank Prof. Andy Borovik and Trenton Parsell (UCI) for assistance with EPR spectroscopy, and Dr. Joe Ziller (UCI) and Dr. Antonio DiPasquale (UCSD) for assistance with X-ray diffraction studies. Funding for this work was provided by NSF-CAREER (CHE-0645685). Supporting Information Available: Detailed experimental procedures, titration calculations, and crystallographic data. This material is available free of charge via the Internet at http:// pubs.acs.org. References (1) Nakamura, N.; Moe¨nne-Loccoz, P.; Tanizawa, K.; Mure, M.; Suzuki, S.; Klinman, J. P.; Sanders-Loehr, J. Biochemistry 1997, 36, 11479. (2) Kishishita, S.; Okajima, T.; Kim, M.; Yamaguchi, H.; Hirota, S.; Suzuki, S.; Kuroda, S.; Tanizawa, K.; Mure, M. J. Am. Chem. Soc 2003, 125, 1041. (3) Kano, K.; Nakagawa, M.; Takagi, K.; Ikeda, T J. Chem. Soc., Perkin Trans. 2 1997, 1111. (4) Blackmore, K. J.; Ziller, J. W.; Heyduk, A. F. Inorg. Chem. 2005, 44, 5559. (5) There is an intermolecular hydrogen bond between apH2 and isqH• in the three-dimensional packing structure. (6) Complete experimental details can be found in the Supporting Information. (7) Bordwell, F. G.; Cheng, J. P.; Ji, G.-Z.; Satish, A. V.; Zhang, X. J. Am. Chem. Soc. 1991, 113, 9790. and references therein. . (8) C ) 73.3 kcal/mol for DMSO and Fc+/Fc reference electrode. See refs 7 and 9. (9) Parker, V. D.; Handoo, K. L.; Roness, F.; Tilset, M. J. Am. Chem. Soc. 1991, 113, 7493. (10) Bordwell, F. G. Acc. Chem. Res. 1988, 21, 456. (11) Titrations with other acids such as CF3COOH gave similar results. (12) Initial titrations of apH2 with lithiated bases such as LiOtBu and LiN(SiMe3)2 yielded inconsistent results, presumably due to coordination of lithium cations to apH2. (13) Bordwell, F. G.; McCallum, R. J.; Olmstead, W. N. J. Org. Chem. 1984, 49, 1424. (14) Lucarini, M.; Pedulli, G. F.; Guerra, M. Chem.—Eur. J. 2004, 10, 933. (15) Direct measurements of the protonation and deprotonation of isqH• are difficult because apH2 (more acidic) and iq (more basic) are always present in the equilibrium mixture. (16) Jovanovic, S. V.; Ko´nya, K.; Scaiano, J. C. Can. J. Chem. 1995, 73, 1803.
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